Chapter 10. Substitution Reactions of Alkyl Halides
Chapter 10. Substitution Reactions of Alkyl Halides
Chapter 10. Substitution Reactions of Alkyl Halides
Chapter 10
Substitution Reactions of Alkyl Halides
Irene Lee Case Western Reserve University Cleveland, OH 2004, Prentice Hall
The atom or group that is substituted or eliminated in these reactions is called a leaving group
+ RCH2 X
X= F, Cl, Br, I
Nu:- +
C X + -
C Nu + X-
Alternatively
C X + C+ + X-
Nu:- +
C+
C Nu
Because a nucleophile substitutes for the halogen, these reactions are known as nucleophilic substitution reactions The reaction mechanism which predominates depends on the following factors: the structure of the alkyl halide the reactivity of the nucleophile the concentration of the nucleophile the solvent of the reaction
Consider the kinetic of the reaction: Rate = k[alkyl halide][nucleophile] a second-order reaction
2. The rate of the reaction with a given nucleophile decreases with increasing size of the alkyl halides 3. The configuration of the substituted product is inverted compared to the configuration of the reacting chiral alkyl halide
A bulky substituent in the alkyl halide reduces the reactivity of the alkyl halide: steric hindrance
Reaction coordinate diagrams for (a) the SN2 reaction of methyl bromide and (b) an SN2 reaction of a sterically hindered alkyl bromide
Inversion of configuration (Walden inversion) in an SN2 reaction is due to back side attack
Carbon and iodide have the same electronegativity Why is RI the most reactive?
UNLIKE
Basicity is a measure of how well a compound (a base) shares its lone pair with a proton Basicity is measured by the acid dissociation constant (Ka)
OH CH3O NH 2 CH3CH2NH
When comparing molecules with attacking atoms of approximately the same size,
When comparing molecules with attacking groups that are very different in size,
more bonding
little bonding
If the reaction is carried out in the gas phase, the stronger bases are the best nucleophiles but, if a protic solvent is used
It is easier to break the ion-dipole interactions between a weak base and the solvent than between a strong base and the solvent
Also, aprotic polar solvents such as DMSO and DMF facilitate the reaction of ionic compounds because they solvate cations
An SN2 reaction proceeds in the direction that allows the strongest base to displace the weaker base
The carbocation reaction intermediate leads to the formation of two stereoisomeric products
When a reaction forms a carbocation intermediate, always check for the possibility of a carbocation rearrangement
Both the cis- and trans-4-methylcyclohexanol are obtained in the SN1 reaction
Benzylic and allylic halides readily undergo SN2, unless they are tertiary
Tertiary benzylic and tertiary allylic halides are unreactive in SN2 because of steric hindrance
Benzylic and allylic halides also undergo SN1 Benzylic and allylic halides form stable carbocations
More than one product may result from an SN1 reaction of an allylic halide
Nu
When an alkyl halide can undergo either SN1 or SN2, the concentration of the nucleophile,